This project aims to elucidate mechanisms controlling growth rate through studies in Long-Evans rat models of experimental growth retardation and catch-up (compensatory) growth. In these models growth retardation is produced by fasting, cortisone injection, or propylthiouracil feeding. Increased responsiveness of pituitary GH release to environmental stimuli found during growth recovery in our recent experiments will be further investigated. During periods of growth retardation and recovery, determination will be made of plasma or serum growth hormone (GH) by radioimmunoassay; somatomedin by porcine cartilage bioassay, cartilage sulfation and synthesis of protein, RNA, and DNA; and pituitary GH content. Plasma GH levels, GH secretory rate, and GH metabolic clearance rates will be measured in intact rats in light and dark periods and also in enucleated rats. Running activity cycles will be monitored in some experiments in order to determine whether the innate 24 hour clock is involved in control of GH release during recovery. Recent findings suggesting the presence of another humoral factor that influences cartilage sulfation during growth recovery. In order to determine the possible role of this factor in the control of growth rate, experiments are planned in recovery rats and in controls parabiosed to treated rats (Buffalo strain) or controls treated with recovery serum. Initially cartilage sulfation and synthesis of protein, RNA, and DNA will be investigated in vitro and in vivo. The cause of previously observed changes of food efficiency for growth and maintenance during growth recovery will be investigated by studies of energy wastage through metabolism or running activity. During this project, light and electron microscopy of cartilage will be carried out in representative animals in order to correlate structure and metabolic findings.